Support is sought for a project intended to further extend application of Fourier transform mass spectrometry to the analysis of high mass and non-volatile biomolecules. Of particular interest are applications to high resolution accurate mass analysis of intractable non-volatile species with masses 2000 to 50,000 daltons and above. The research will utilize a unique Nicolet 7.2 Tesla FTMS-2000 dual cell FTMS instrument. A modified dual-cell 3 Tesla FTMS- 1000 instrument equipped with supercritical fluid, high performance liquid chromatography, and gas chromatography interfaces, and a single cell 3 Tesla FTMS- 1000 instrument are also available for the research, if needed. Primary goals of the proposed research include investigation of high resolution matrix-assisted laser desorption mass spectrometry of high mass biomolecules and development of efficacious means of obtaining structural information on biomolecules. Alternatives to collision-induced dissociation (which is not consistently effectual in the energy regime available for FTMS or for molecules with masses above 1500 amu) will be investigated. Specific topics to be investigated include: (1) matrix-assisted ultraviolet and infrared laser desorption; (2) laser desorption/photodissociation methods; (3) use of in situ derivatization methods to incorporate metals to serve as analytical chromophores within analytes of interest; and (4) surface-induced dissociation of laser-desorbed ions. It is expected that this research will result in improved understanding of fundamental processes and constraints governing the analysis of high mass molecular species with masses in the 2000 - 100,000 dalton range. A number of analytically useful methods permitting application of FTMS to biomolecule structure determination are expected to result.